Báo cáo sinh học: " Predicting the consequences of selecting on PrP genotypes on PrP frequencies, performance and inbreeding in commercial meat sheep populations" doc

Genet Sel Evol 39 (2007) 711–729 c INRA, EDP Sciences, 2007 DOI: 10.1051/gse:2007027 Available online at: www.gse-journal.org Original article Predicting the consequences of selecting on PrP genotypes on PrP frequencies, performance and inbreeding in commercial meat sheep populations Wing-Young N Mana∗ , Ronald M Lewisb , Kay Boultonc , Beatriz Villanuevaa b a Scottish Agricultural College, West Mains Road, Edinburgh, EH9 3JG, UK Department of Animal and Poultry Sciences (0306), Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA c Meat & Livestock Commission, Snowdon Drive, Milton Keynes, MK6 1AX, UK (Received 12 January 2007; accepted June 2007) Abstract – Selection programmes based on prion protein (PrP) genotypes are being implemented for increasing resistance to scrapie Commercial meat sheep populations participating in sire-referencing schemes were simulated to investigate the effect of selection on PrP genotypes on ARR and VRQ allele frequencies, inbreeding and genetic gain in a performance trait under selection PrP selection strategies modelled included selection against the VRQ allele and in favour of the ARR allele Assuming realistic initial PrP frequencies, selection against the VRQ allele had a minimal impact on performance and inbreeding However, when selection was also in favour of the ARR allele and the frequency of this allele was relatively low, there was a loss of up to three to four years of genetic gain over the 15 years of selection Most loss in gain occurred during the first five years In general, the rate of inbreeding was reduced when applying PrP selection Since animals were first selected on their PrP genotype before being selected on the performance trait, the intensity of selection on performance was weaker under PrP selection (compared with no PrP selection) Eradication of the VRQ allele or fixation of the ARR allele within 15 years of selection was possible only with PrP selection targeting all breeding animals sire referencing / scrapie / prion / PrP selection / inbreeding INTRODUCTION Several countries are currently implementing breeding programmes for increasing resistance to scrapie [1, 6, 7, 9–12, 28] In most of these programmes, ∗ Corresponding author: nicola.man@sac.ac.uk SLS Group, SAC, Bush Estate, Penicuik, Midlothian EH26 OPH, Scotland, UK Article published by EDP Sciences and available at http://www.gse-journal.org or http://dx.doi.org/10.1051/gse:2007027 712 W.-Y.N Man et al selection is based on polymorphisms at codons 136, 154 and 171 of the gene encoding the prion protein (PrP), which are associated with susceptibility to the disease [16] These polymorphisms jointly define the PrP alleles In general, these programmes aim at eliminating the VRQ allele and increasing the frequency of the ARR allele The effectiveness of such breeding programmes for increasing the frequency of resistant alleles has been investigated in mainstream commercial e.g [2,3,21,22] and numerically small breeds e.g [11,15,28] Four of the studies also assessed the impact of selection on PrP genotypes on inbreeding and genetic variability [2, 11, 21, 28] Selection on PrP genotypes could, additionally, have negative consequences on genetic progress for other economically important traits and, potentially, on inbreeding in commercial populations In the UK as well as in other countries, sire-referencing schemes (SRS) had been established for commercial sheep populations in order to allow comparisons across co-operating flocks In SRS, genetic links are created among flocks by the sharing of some rams (reference sires) These connections allow for across-flock genetic evaluations creating a larger pool of candidates for selection The objective of this study was to assess, through Monte Carlo computer simulation, the impact of various PrP selection strategies on changes in PrP allele frequencies, inbreeding and genetic gain in performance traits, in meat sheep populations typical of those participating in SRS METHODS 2.1 Genetic model The trait under selection was a performance trait, such as lean growth, for which an infinitesimal model and a moderate heritability (0.25) were assumed It was recorded in both sexes before selection for breeding The PrP gene was assumed to have no direct impact on the trait and to be unlinked with genes that influence this trait 2.2 Breeding schemes The simulations modelled the operation of SRS in the three major meatproducing breed types in the UK, i.e terminal sire, crossing sire and hill sheep [3, 25] Hill breeds are kept in harsh hill areas and the ewes usually breed for four lamb crops Older ewes of these breeds are then moved to less harsh upland areas where they are crossed with longwool sires (crossing sires) 713 Consequences of PrP selection Table I Simulation parameters for terminal sire, crossing sire, and hill breeds Number of flocks Number of ewes per flock Total number of ewes per year Percentage of within-flock sires replaced per year Number of reference sires replaced per year Number of reference sires used per year per flock Percentage of ewes producing lambs from reference sires Terminal sire Crossing sire Hill 15 13 17 40–140 30–90 100–700 1030 600 6800 50 3 31 50 2 30 60 2 Within-flock sire:ewe ratio 1:20 1:20 1:40 Generation interval Male Female 3.0 3.5 2.8 3.4 2.2 3.8 Average litter size at birth at weaning 1.7 1.5 2.2 1.6 1.5 1.3 The resulting crossbred ewes are usually mated in lowland areas to rams of terminal sire breeds, which have good carcass characteristics In general, SRS for terminal sire breeds were modelled as described by Lewis and Simm [18] Simulations of crossing sire and hill breeds followed the same model, but with different inputs for genetic, reproductive, survival and flock parameters Table I summarises the most relevant parameters used in the simulation of the three breed types Populations were simulated over a 30 year period Sire referencing started in year six, after five years of random selection Selection on PrP genotype started in year 16, after ten years of sire referencing Year t = will refer to the year PrP selection began, so that year t = –15 will refer to the base population (in which all animals were unrelated), and year t = 15 will refer to the last year of the simulation Animals were assumed to reach reproductive maturity at about two years of age, and breeding animals were selected when they were about one year old From t = –10 (when sire referencing began) onwards, replacement ewes and rams were selected based on estimated breeding values (EBV) for performance obtained from best linear unbiased prediction (BLUP) There was one mating season per year that lasted three oestrus cycles The overall conception rate was about 90% for all breed types Litter size was modelled as described by Lewis and Simm [18] Survival rates at various ages (which included accounting for involuntary culling) were derived based on 714 W.-Y.N Man et al estimates of the proportion of males and females at various ages in UK populations Dams were only used within their flock of birth for a maximum of four (terminal sire) or five years (crossing sire and hill) About 25% of dams were replaced annually Two types of sires were used: within-flock sires which were only used within the flock in which they were born, and reference sires which were used across all flocks when SRS was implemented (i.e from t = –10 onwards) In contrast to the scheme modelled by Lewis and Simm [18], only rams born within the scheme were used Within-flock sires were used for a maximum of three (terminal and crossing sires) or two (hill) consecutive years Fifty (terminal and crossing sires) or 60% (hill) of the within-flock sires were replaced annually with new rams The sires to be replaced were chosen at random There were no restrictions on selection of family members for replacement ewes and within-flock rams, but full-sibs and half-sibs were avoided in the selection of replacement rams for the reference sire team During the years of sire referencing (t = –10 to t = 15), a team of six (terminal sire), three (crossing sire) or two (hill) reference sires were used each year In the terminal and crossing sire scenarios, reference sires were used for a maximum of two consecutive years Three of the team of six reference sires (the three oldest sires in the team) were replaced every year in terminal sire breeds, and two (randomly chosen) of the team of three were replaced in crossing sire breeds In hill breeds, reference sires were replaced every year In terminal sire breeds, ten ewes were artificially inseminated in their first oestrus cycle to each of three reference sires (drawn at random from the team of six) in every flock and year In crossing sire and hill breeds, ten and sixteen ewes, respectively, were artificially inseminated in their first oestrus cycle to each of two reference sires in every flock and year Natural mating was practised for within-flock sires Surplus ewes (i.e those not artificially inseminated with a reference sire) and all ewes in the second and third oestrus that failed to conceive in the first oestrus (including those that failed after artificial insemination with a reference sire) were mated to within-flock rams The within-flock ram:(surplus) ewe mating ratio and the percentage of breeding ewes producing lambs from reference sires for each breed type are shown in Table I All matings were at random 2.3 Initial frequencies of PrP alleles and selection strategies Initial (at t = 0) allele frequencies simulated were 0.05, 0.30 and 0.70 for ARR (recognised to be the allele conferring most resistance to classical Consequences of PrP selection 715 scrapie) and 0.05, 0.15 and 0.30 for VRQ (the most susceptible allele) These were based on the ranges estimated by Eglin et al [13] The specific combinations of ARR and VRQ frequencies simulated are given in the results (see later) The other alleles (xxx) made up for the remainder segregating in the population The PrP selection strategies modelled were the following: (1) only animals with no VRQ allele could be used for breeding (strategy S1); (2) only animals with at least one ARR allele and no VRQ allele could be used for breeding (strategy S2); or (3) all animals could be used for breeding, but they were sequentially selected on their genotype using the following priority – ARR/ARR, ARR/xxx, xxx/xxx (i.e those without ARR or VRQ), ARR/VRQ, VRQ/xxx, and VRQ/VRQ (strategy S3) Within each of these strategies, different groups of breeding animals were targeted for PrP selection: (1) reference sires (strategies S1R , S2R and S3R ); (2) all sires, i.e reference sires as well as within-flock sires (strategies S1RW , S2RW and S3RW ); or (3) all breeding animals, i.e all sires and breeding ewes (strategies S1RWD , S2RWD and S3RWD ) The PrP genotype of all targeted animals was assumed to be known When applying PrP selection strategies, only new breeding animals (reference sires, all sires or all sires and breeding ewes, depending on the strategy simulated) were selected based on their PrP genotype and they were then subsequently selected on their EBV for the performance trait For instance, when S3 was applied, the first animals selected were those with the ARR/ARR genotype If the number of homozygous ARR was higher than that required to be selected for breeding then animals within the ARR/ARR group were chosen according to their EBV Equivalently, animals with the highest EBV of those not carrying the VRQ allele (S1) or of those carrying at least one ARR allele and no VRQ allele (S2) were selected for breeding These strategies were compared to the scenario where there was no selection on PrP, but animals were selected on the performance trait EBV (NS) Comparisons were in terms of ARR and VRQ frequencies (fARR and fVRQ , respectively) and rates of genetic gain (for the performance trait) and inbreeding Average true breeding value for the performance trait (Gi ) and average inbreeding (Fi ) of animals born at each year i were computed Rates of gain (ΔGi ) and inbreeding (ΔFi ) were obtained every year as ΔGi = Gi − Gi−1 and ΔFi = (Fi − Fi−1 )/(1 − Fi−1 ), respectively Annual rates between years i and j (ΔGi−j and ΔFi−j , where j > i) were obtained by averaging the individual annual rates One hundred Monte Carlo replicates were run for each scenario Values presented are the averages over all replicates 716 W.-Y.N Man et al RESULTS 3.1 Changes in frequency of the VRQ allele Changes in fVRQ for strategies S1R , S1RW , S1RWD and NS are shown in Figure for the three breed types when the initial fVRQ was 0.05, 0.15 or 0.30 Corresponding values for fARR were 0.70, 0.30 and 0.05 but changes in fVRQ were unaffected by the initial value of fARR As expected, there was no change in fVRQ when selection was only on performance (NS) When PrP selection was only applied to reference sires (strategy S1R ), the rate at which fVRQ decreased in hill populations was about half that observed in the other two breed types since, proportionally, substantially fewer ewes were mated to reference sires in hill populations At t = 10, fVRQ was approximately half the initial fVRQ in both terminal and crossing sire populations but only about 3/4 of the initial fVRQ in hill populations Changes in fVRQ were practically the same for terminal and crossing sire populations except in the first year of PrP selection where the decrease in fVRQ was larger in crossing sire scenarios, particularly with selection targeted to reference sires only (S1R ) This was due to the different proportion of reference sires retained in the two breeds and potentially carrying the VRQ allele at time t = (1 /3 of the reference sire team was retained in the crossing sire and /2 was retained in the terminal sire) In subsequent years, all sires in the reference sire team would already have been replaced with non-VRQ carrier sires, and fVRQ was very similar in both breed types In all breed types, when selection was on all sires (S1RW ) fVRQ halved after two years of PrP selection and then approximately halved every four years None of the 100 replicates for those scenarios targeting only the sires (i.e S1R and S1RW ) led to the loss of the VRQ allele from the population within the 15 years of selection In the terminal sire simulations with initial fVRQ of 0.15, fVRQ at t = 15 ranged across replicates from 0.01 to 0.12 for S1R and from